1. Field of the Invention
The present invention involves the field of Magnetic Resonance Imaging (MRI). Particularly, the present invention involves the use of MR signal information from a reference substance identified within an MR image to provide quantitative Magnetization Transfer weighted (MTw) images. More particularly, the present invention involves the use of MR signal corresponding to cerebrospinal fluid (CSF) as a reference to provide quantitative MTw images of the spinal cord.
2. Discussion of the Related Art
Certain neurological diseases, such as Adrenomyeloneuropathy (AMN), Multiple Sclerosis (MS), genetic leukodystrophies, and Amyotrophic Lateral Sclerosis (ALS), involve a breakdown of the myelin sheath present in white matter of central nervous system tissue. Such demyelination can become apparent within the spinal cord before becoming apparent in the brain, and before becoming detectable via conventional (T1w, T2w) MRI techniques. As such, early diagnosis of these diseases may be achieved by identifying and quantitatively assessing the breakdown of myelin found in white matter within the spinal cord.
In addition to diagnosing demyelinating diseases, quantitative assessment of the breakdown of myelin within the spinal cord may be used to determine the effect of trauma to the spinal cord.
Magnetization Transfer Ratio (MTR) imaging is a known MRI technique that is often used for imaging and quantifying the extent of white matter diseases in the brain and spinal cord. MTR imaging involves acquiring two MR images, one with and one without off-resonance (with respect to water) radiofrequency (RF) saturation of the solid-like, macromolecular proton species (or solid phase protons, hereinafter “solid component”) present in the target tissue. The image acquired in the absence of RF saturation is referred to as the reference image, while the image acquired with RF saturation is referred to as the saturation image or MT weighted (MTw) image. As used herein, “imagery” may refer to a single image, or multiple images taken at different times or corresponding to different characteristics, such as RF frequency.
Tissue containing solid-like macromolecular proton species, i.e., solid components, within the target tissue can be preferentially saturated by an off-resonance (different irradiation frequency with respect to the water frequency) RF pulse. This so-called magnetization transfer (MT) prepulse or preparation pulse partially saturates the solid proton pool, and this saturation is subsequently transferred to free water protons, which are imaged by conventional MRI techniques. White matter has a greater density of solid-like macromolecular protons than grey matter (due to its large proportion of myelin) and thus will transfer more saturation to the free water protons, leading to a greater magnetization transfer (MT) effect. Computing the voxel-by-voxel ratio of the two images (saturation over reference) provides a quantitative assessment, of the sensitivity of the MT effect in different tissues contributing to the image, e.g. white matter vs. grey matter. MTR imaging is discussed in further detail in U.S. Pat. No. 5,050,609 to Balaban et al., which is incorporated by reference as if fully disclosed herein.
As mentioned above, MTR images are obtained by performing a reference scan and a saturation scan. A normalized signal response is then computed according to the following relation:
                                                        M              z                        ⁡                          (              ω              )                                            M            o                          =                  1          -                      M            ⁢                                                  ⁢            T            ⁢                                                  ⁢            R                                              (        1        )            where Mz(ω) is the signal corresponding to a given voxel taken during the saturation scan at the irradiation frequency ω; Mo is the signal corresponding (ideally) to the same voxel taken during the reference scan; and MTR refers to the Magnetization Transfer Ratio of the target tissue within the voxel.
Problems associated with the related art include the following. First, motion induced errors between the reference scan and the saturation scan limit the quality of the computed MTR. Second, coil loading effects of the MR scanner affect the repeatability of typical MTw images for a given patient, therefore, while the extent of demyelination may be determined for a given patient at a single time point using MTw imaging, it is generally not possible to quantitatively track the progression of the disease for a given patient with MTw imaging alone.
Motion control-induced errors result from the fact that Mz(ω) and Mo are taken from two different images that are acquired at different times. Since these two signals are acquired during two different scans that are temporally separated, the voxels must be co-registered, which results in uncertainty in their correspondence if the co-registration is not perfect. Any motion of the target tissue between these scans reduces the precision of the Magnetization Transfer Ratio, and thus decreases the Signal to Noise Ratio (SNR) of the resultant MT image and dilutes the quantitative assessment of the tissue MT effect. Out of plane motion between image acquisitions is particularly problematic in that image manipulation cannot register voxels corresponding to tissue regions that have moved into, or out of, the image plane between image acquisitions.
Related art solutions that attempt to compensate for motion of the target tissue include sophisticated image registration algorithms, which use feature recognition to map one image onto another so that a voxel-by-voxel MTR may be computed with some acceptable precision. As such, related art motion compensation techniques generally improve the quality of MTR images of the brain. Although MTR assessment is quite robust with regard to the brain, it has not been very successful in assessing the spinal cord.
There are problems associated with the related art motion compensation techniques, which make quantitative assessment of the spine prohibitively difficult. For example, the spinal cord has much smaller (spinal cord diameter at cervical vertebra C2˜1.5 cm) structures than the brain. The dorsal and lateral columns of the cervical spinal cord are of particular interest as they carry vibration sensitivity and motion impulses to and from the extremities, respectively. As such, obtaining precise MTR images of these regions is important in diagnosing many of the aforementioned diseases. However, discriminating white and grey matter structures within the spinal cord generally requires a transverse spatial resolution between 0.5 mm and 2 mm. Such high-resolution imaging increases the motion sensitivity. Given the smaller features of the spinal cord, such as the spinal cord tracts which are separated by the sub-centimeter grey matter horns, related art motion compensation techniques have been found to often be inadequate for registering two sequentially acquired MR images. This makes related art MTR imaging of the spinal cord at spatial resolutions required for early visualization of demyelinating diseases prohibitively unreliable. As such, related art applications of MTR imaging of the spinal cord are generally limited to identifying large scale effects of demyelinating diseases by imaging large inflammatory lesions within the spinal cord, and generally require a priori information pertaining to the location and etiology of the particular disease.
Second, it is possible to obtain high resolution, high SNR MTw images in the spinal cord, but MTw imagery alone is confounded by coil loading effects of the MR scanner making MTw imaging qualitative, but not quantitative. Any RF coil within an MR scanner has a gain pattern, which results in a position-dependent sensitivity. As such, repeatability between successive MTw images requires that the target tissue be located at the same location within the RF coil's gain pattern for each image acquisition, which is unlikely. Further, coil loading (electromagnetic interaction between the patient and the RF coil) limits the repeatability of successive MTw image acquisition. This is because the sensitivity of the MR scanner, and thus the resultant MTw values, changes temporally, which prevents quantitative inter-MTw image comparison for a given patient, unless properly normalized.
For at least these reasons, there is a strong need for high-SNR motion-insensitive MT imagery, which is repeatable, which may be quantitatively assessed with respect to a control subject, and which has sufficient spatial resolution to discern white matter structures and to separate these structures from the surrounding grey matter within the spinal cord.